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ID PMID Title PublicationDate abstract
27468372 Distal Radius Hemiarthroplasty. 2016 Aug INTRODUCTION: Due to a higher risk for implant loosening, particularly of the distal component, patients with physically demanding lifestyles are infrequently considered for total wrist arthroplasty (TWA). A distal radius hemiarthroplasty may obviate the need for the strict restrictions recommended for patients treated by TWA, thus providing another surgical option for active patients with severe wrist arthritis, especially those with articular degeneration of the lunate facet of the radius, capitate head, or combination of both, who are not typically candidates for traditional motion-preserving procedures. MATERIALS AND METHODS: Eight fresh-frozen cadaver limbs (age range, 43-82 years) with no history of rheumatoid arthritis or upper extremity trauma were used. Radiodense markers were inserted in the radius and hand. Posteroanterior (PA) fluoroscopic images with the wrist in neutral, radial deviation, and ulnar deviation, and lateral images with the wrist in neutral, flexion, and extension were obtained for each specimen before implantation, after distal radius hemiarthroplasty, and after combined hemiarthroplasty and PRC. RESULTS: On the PA images, the capitate remained within 1.42 and 2.21 mm of its native radial-ulnar position following hemiarthroplasty and hemiarthroplasty with PRC, respectively. Lateral images showed the capitate remained within 1.06 mm of its native dorsal-volar position following hemiarthroplasty and within 4.69 mm following hemiarthroplasty with PRC. Following hemiarthroplasty, capitate alignment changed 2.33 and 2.59 mm compared with its native longitudinal alignment on PA and lateral films, respectively. These changes did not reach statistical significance. As expected, significant shortening in longitudinal alignment was seen on both PA and lateral films for hemiarthroplasty with PRC. CONCLUSION: A distal radius implant hemiarthroplasty with or without a PRC provides good static alignment of the wrist in a cadaver model and thus supports the concept as potential treatment alternatives for advanced wrist arthritis; however, combined hemiarthroplasty with a PRC has more clinical relevance because it avoids the risk of proximal carpal row instability and eliminates the commonly arthritic radioscaphoid joint.
26290328 Abatacept decreases disease activity in a absence of CD4(+) T cells in a collagen-induced 2015 Aug 20 INTRODUCTION: Abatacept is a fusion protein of human cytotoxic T-lymphocyte-associated protein (CTLA)-4 and the Fc portion of human immunoglobulin G1 (IgG1). It is believed to be effective in the treatment of rheumatoid arthritis by inhibiting costimulation of T cells via blocking CD28-B7 interactions as CTLA-4 binds to both B7.1 (CD80) and B7.2 (CD86). However, the interaction of CD28 with B7 molecules is crucial for activation of naive cells, whereas it is unclear whether the action of already activated CD4(+) T cells, which are readily present in established disease, also depends on this interaction. The aim of this study was to determine whether the mode of action of abatacept depends solely on its ability to halt T cell activation in established disease. METHODS: Arthritis was induced in thymectomized male DBA/1 mice by immunisation with bovine collagen type II. The mice were subsequently depleted for CD4(+) T cells. Abatacept or control treatment was started when 80 % of the mice showed signs of arthritis. Arthritis severity was monitored by clinical scoring of the paws, and anti-collagen antibody levels over time were determined by enzyme-linked immunosorbent assay. RESULTS: Treatment with abatacept in the absence of CD4(+) T cells resulted in lower disease activity. This was associated with decreasing levels of collagen-specific IgG1 and IgG2a antibodies, whereas the antibody levels in control or CD4(+) T cell-depleted mice increased over time. CONCLUSIONS: These results show that abatacept decreased disease activity in the absence of CD4(+) T cells, indicating that the mode of action of abatacept in established arthritis does not depend entirely on its effects on CD4(+) T cell activation.
26677159 Juvenile spondyloarthropathy: an important clinical lesson to remember. 2015 Dec 16 Spondyloarthropathy (SpA) is a group of inflammatory conditions that include spondylitis, sacroiliitis, asymmetrical peripheral arthritis and enthesitis. This condition is known as juvenile SpA when the diagnosis is made in patients up to 16 years of age. Enthesitis is a highly specific feature that occurs more often in juvenile SpA than in the adult form. In contrast to adult onset SpA, the initial manifestation of juvenile SpA rarely presents as inflammatory back pain. Peripheral arthritis is the more common presenting feature. We report a case of a 12-year-old boy who presented with a 1-year history of progressive low back pain, gluteal pain and thigh pain. There were no clinical symptoms of arthropathy of the distal extremities. MRI of the whole spine was performed twice, which, unfortunately, was unyielding. Finally, MRI of the sacroiliac joints revealed asymmetric sacroiliitis as well as enthesitis of the hips and pelvis. Further laboratory data showed negative rheumatoid factor and positive human leucocyte antigen (HLA) B27. A diagnosis of juvenile SpA with sacroiliitis and enthesitis was made. The imaging characteristics of juvenile SpA are highlighted.
25220674 Impact of medication withdrawal method on flare-free survival in patients with juvenile id 2015 May OBJECTIVE: To determine whether order of medication withdrawal in children with juvenile idiopathic arthritis (JIA) taking methotrexate (MTX) and tumor necrosis factor inhibitor (TNFi) combination therapy (CBT) affects flare-free survival (FFS). METHODS: This retrospective observational study of 335 patients with polyarticular JIA or enthesitis-related arthritis analyzed FFS off medications in 4 withdrawal arms: 1) TNFi plus MTX, off MTX first, 2) TNFi plus MTX, off TNFi first, 3) MTX monotherapy, or 4) TNFi monotherapy. Outcomes were evaluated based on order of medication withdrawal, clinical presentation, serologic parameters, and duration of clinically inactive disease (CID) while taking medications. RESULTS: Sixty-four percent of all patients achieved CID. However, 89% of patients on CBT who withdrew TNFi first flared within 12 months despite continuing MTX, compared to 12% of those who withdrew MTX and continued TNFi (P < 0.0005). Twenty-seven percent of patients discontinued all medications, but 63% flared within 12 months, and only 49% of these regained CID within 12 months of restarting therapy. Patients on MTX monotherapy had the best FFS after medication withdrawal. FFS was independent of disease subtype, rheumatoid factor status, initial erythrocyte sedimentation rate, initial joint count, corticosteroid exposure, time in CID, and method of medication discontinuation. CONCLUSION: This study confirms that flare rates in JIA are high, and discontinuing medications is challenging. Withdrawal of TNFi from CBT first carries a significantly higher risk of disease flare than withdrawing MTX first. The high relapse rate after discontinuation of TNFi suggests that these medications may not modify the underlying disease process.
25940873 [Juvenile rheumatoid diseases: Endoprosthetic care of destroyed hip joints]. 2015 Jul BACKGROUND: Patients with juvenile idiopathic arthritis (JIA) often suffer from involvement of the hip joints, with joint destruction and related functional limitations, making hip replacement necessary. OBJECTIVES: To discover what special features are to be expected in patients with JIA and hip arthroplasty and what impact they have on surgical indication, choice of implant, and technique. METHODS: Selective literature review and evaluation of our patient population. RESULTS: Compared with osteoarthritis patients, JIA patients are on average much younger at the time of hip replacement. Owing to the onset of the disease in childhood or adolescence and the frequent glucocorticoid therapy, growth disorders or abnormal anatomical findings are common in these patients. Bone density is often reduced at an early age. The perioperative management of medication has to be planned. Special implants for patients with rheumatic diseases do not exist, but the above peculiarities of this group of patients should be considered for surgical procedure and choice of implant and material. Overall, the results of hip arthroplasty in juvenile rheumatic diseases, in terms of pain relief and functional improvement, are good. The limited life of the arthroplasty is problematic. CONCLUSIONS: By relieving pain, improvement of the range of motion and activity level very high patient satisfaction is usually achieved by hip arthroplasty in JIA patients. In the case of involvement of the contralateral hip or the ipsilateral knee joint it may be useful to perform a simultaneous, single-stage joint replacement of both joints.
27654603 Non-TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patie 2016 Sep 20 IMPORTANCE: One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor α (TNF-α) inhibitors; little guidance on choosing the next treatment exists. OBJECTIVE: To compare the efficacy of a non-TNF-targeted biologic (non-TNF) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor. DESIGN, SETTING, AND PARTICIPANTS: A total of 300 patients (conducted between 2009-2012) with rheumatoid arthritis, with persistent disease activity (disease activity score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR]  ≥ 3.2 [range, 0-9.3]) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter, pragmatic, open-label randomized clinical trial. The final follow-up date was in August 2013. INTERVENTIONS: Patients were randomly assigned (1:1) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment. The choice of the biologic prescribed within each randomized group was left to the treating clinician. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism (EULAR) scale at week 24. Secondary outcomes included the EULAR response at weeks 12 and 52; at weeks 12, 24, and 52; DAS28ESR, low disease activity (DAS28 ≤3.2), remission (DAS28 ≤2.6); serious adverse events; and serious infections. RESULTS: Of the 300 randomized patients (243 [83.2%] women; mean [SD] age, 57.1 [12.2] years; baseline DAS28-ESR, 5.1 [1.1]), 269 (89.7%) completed the study. At week 24, 101 of 146 patients (69%) in the non-TNF group and 76 (52%) in the second anti-TNF group achieved a good or moderate EULAR response (OR, 2.06; 95% CI, 1.27-3.37; P = .004, with imputation of missing data; absolute difference, 17.2%; 95% CI, 6.2% to 28.2%). The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group (mean difference adjusted for baseline differences, -0.43; 95% CI, -0.72 to -0.14; P = .004). At weeks 24 and 52, more patients in the non-TNF group vs the second anti-TNF group showed low disease activity (45% vs 28% at week 24; OR, 2.09; 95% CI, 1.27 to 3.43; P = .004 and 41% vs 23% at week 52; OR, 2.26; 95% CI, 1.33 to 3.86; P = .003). CONCLUSIONS AND RELEVANCE: Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01000441.
25439190 Parthenolide inhibits pro-inflammatory cytokine production and exhibits protective effects 2015 May OBJECTIVES: Progressive destruction of synovial joint cartilage and bone occurs in pathological conditions such as rheumatoid arthritis (RA) because of the overproduction of pro-inflammatory cytokines and activation of nuclear factor kappa B (NF-κB). Through the screening of NF-κB inhibitors by a luciferase reporter gene assay, we identified parthenolide (PAR) as the most potent NF-κB inhibitor, among several PAR analogue compounds. This study was undertaken to determine whether PAR inhibits pro-inflammatory cytokine production, cartilage degradation, and inflammatory arthritis. METHOD: The mRNA levels of pro-inflammatory cytokines were examined by real-time polymerase chain reaction (PCR). Proteoglycan content and release were determined by measuring glycosaminoglycan (GAG) levels using the dimethylmethylene blue (DMMB) dye-binding assay. The potential role of PAR in treatment of arthritis was studied using a collagen-induced arthritis (CIA) model. RESULTS: We established that PAR, as a prototype compound, suppressed lipopolysaccharide (LPS)- and tumour necrosis factor (TNF)-α-induced increases in matrix metalloproteinase (MMP)-1, MMP-3, inducible nitric oxide synthase (iNOS), and interleukin (IL)-1β mRNA in chondrocytes. In addition, PAR prevented proteoglycan degradation triggered by pro-inflammatory cytokines. PAR treatment at the onset of CIA symptoms significantly reduced synovitis, inflammation, and pannus formation scores. Reduced synovial inflammation after PAR treatment was also reflected in significantly less bone erosion and cartilage damage. CONCLUSIONS: These data indicate a protective effect of PAR on the catabolic insults of pro-inflammatory cytokines on chondrocyte metabolism and GAG release in vitro and in CIA. PAR had anti-inflammatory and structure-modifying effects on experimental arthritis, suggesting that PAR may be useful as a potential alternative or adjunct therapy for inflammatory arthritis.
25742802 Prevalence of overweight in children and adolescents with juvenile idiopathic arthritis. 2015 OBJECTIVES: To assess the prevalence of overweight in patients with juvenile idiopathic arthritis (JIA) between 2003 and 2012 and to determine correlates of overweight relevant to the change in the overweight rate. METHOD: Annual overweight prevalence was determined in the National Paediatric Rheumatological Database (NPRD) between 2003 and 2012. The prevalence of overweight in JIA was compared to representative data from Germany in 2005. RESULTS: The median age of JIA patients was 11.5 years and the mean disease duration 4 years. Almost 50% of JIA patients had persistent oligoarthritis, followed by rheumatoid factor (RF)-negative polyarthritis (14%). The overweight prevalence decreased significantly from 14.2% in 2003 to 8.3% in 2012 [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.89-0.95]. Higher levels of physical activity and less frequent treatment with high-dose glucocorticoids (GCs) were associated with decreasing overweight rates. Systemic JIA had the highest decrease in the overweight rate over time. Patients with JIA had an overweight rate comparable to that of children and adolescents in the general population. However, systemic JIA and enthesitis-related arthritis were more likely to be associated with overweight. The use of high-dose GCs, lower functional limitations, and a lower level (or lack) of participation in school sports were significant predictors of overweight in multivariable analyses. CONCLUSIONS: The prevalence of overweight in JIA was comparable to the general population and decreased significantly over time. The decrease was associated with higher functional ability and JIA patients should be encouraged to be more physically active. The role of an elevated body mass index (BMI) in the long-term outcome of JIA needs to be addressed in future studies.
25689950 Evaluation of anti-inflammatory, anti-nociceptive, and anti-arthritic activities of Indian 2015 Apr Traditionally venoms are used from thousands of years to treat pain, inflammation, and arthritis. In Ayurveda "Suchika Voron" and "Shodhona" were practiced against pain. In the present study, venom composition of the Indian honeybee Apis florea (AF), Apis dorsata (AD), and Apis cerana indica (AC) were analyzed using electrophoresis (SDS-PAGE). This venom analysis was used to shed light upon the correlation in structure and the venom composition among the three species in Indian fields. Among the three species, Indian Apis dorsata bee venom (ADBV) is evaluated for an anti-inflammatory, anti-nociceptive activity, and antiarthritic activity in different animal models. The effect of ADBV is revealed for its anti-arthritic activity in the FCA- and CIA-induced arthritis model in male Wistar rats. The immunosuppressant action of ADBV was studied by hemagglutination antibody titer. It has been found that ADBV possesses anti-inflammatory and antinociceptive activities. In FCA- and CIA-induced arthritis, ADBV able to decrease rheumatoid factor, pain perception parameters, C-reactive protein, erythrocytes sedimentation rate, urinary hydroxyproline, serum transaminase level, and serum nitric oxide level when compared with diseased control arthritic rats. IL-6, TNF-α level was found to be decrease by ADBV treatment in collagen induced arthritis model. Thus this study confirmed the scientific validation behind utilization of venom in Indian Apis dorsata bees in arthritis and inflammatory diseases which has been not reported till date.
26796310 Association of Intraocular Pressure Changes With Right Ventricular Diameter and Brain Natr 2016 Mar PURPOSE: To report a case of secondary pulmonary arterial hypertension (PAH) and the relationship of intraocular pressure (IOP) change with right ventricular diameter (RVD) and brain natriuretic peptide (BNP). METHODS: Case report. PATIENT: A 22-year-old woman with dilated and congested conjunctival and episcleral veins was diagnosed with high IOP. She was previously diagnosed with Sjögren syndrome and suffered from secondary PAH. RESULTS: The RVD and BNP level improved and the IOP decreased with routine treatment for PAH. During self-cessation of treatment for PAH, the RVD, BNP level, and IOP deteriorated. However, they improved after treatment was reinitiated. CONCLUSION: There was a synchronizing change in the parameters representing high pulmonary arterial pressure and IOP during treatment of PAH.
26790457 Exploring BAFF: its expression, receptors and contribution to the immunopathogenesis of Sj 2016 Sep SS is an autoimmune condition characterized by exocrine gland destruction, autoantibody production, immune complex deposition and systemic complications associated with lymphocytic infiltration of many organs. Genetic, environmental and viral factors play a role in disease aetiology, however, the exact mechanisms driving the immunopathogenesis of SS remain uncertain. Here we discuss a role for B cell activating factor (BAFF), whereby B cell hyperactivity and increased BAFF secretion observed in patients and animal models of the disease can be explained by the altered expression of cell-specific BAFF/BAFF receptor (BAFF-R) variants in several immune cell types. Understanding the role of BAFF/BAFF-R heterogeneity in SS pathogenesis could help to facilitate new treatment strategies for patients.
27107430 Cryoglobulinaemic vasculitis at diagnosis predicts mortality in primary Sjögren syndrome: 2016 Aug OBJECTIVE: To evaluate the fulfilment of classification criteria for cryoglobulinaemic vasculitis (CV) at diagnosis in a large cohort of patients with primary SS and their correlation with poor outcomes. METHODS: We included 515 consecutive patients tested for serum cryoglobulins who fulfilled the 2002 classification criteria for primary SS. CV classification criteria and serum cryoglobulins at diagnosis were assessed as predictors of death and lymphoma using Cox proportional-hazards regression analysis adjusted for age and gender. RESULTS: Positive serum cryoglobulins were detected in 65 (12%) patients, of whom 21 (32%) fulfilled CV classification criteria. Compared with patients positive for cryoglobulins who did not fulfil CV criteria, patients with CV had a higher frequency of type II cryoglobulinaemia (86% vs 43%, P = 0.04), a higher mean cryocrit level (6.58% vs 1.25%, P < 0.001) and a higher cumulated mean EULAR-SS disease activity index score (35.3 vs 16.2, P < 0.001). After a mean follow-up of 110 months, 45 (9%) patients developed B-cell lymphoma and 33 (6%) died. Compared with patients without cryoglobulins, patients with cryoglobulins who fulfilled [hazard ratio (HR) = 7.47, 95% CI: 3.38, 16.53] and did not fulfil (HR = 2.56, 95% CI: 1.03, 6.35) CV criteria both showed a higher risk of B-cell lymphoma in the univariate analysis, but not in the multivariate models. Compared with patients without cryoglobulins, patients with CV had a higher risk of death in both the univariate (HR = 11.68, 95% CI: 4.44, 30.74) and multivariate (HR = 4.36, 95% CI: 1.32, 14.47) models. CONCLUSION: Patients with primary SS who fulfilled criteria for cryoglobulinaemic vasculitis at diagnosis are at higher risk of death.
26276967 Relation of Autoimmune Cytopenia to Glandular and Systemic Manifestations in Primary Sjög 2015 Oct OBJECTIVE: To investigate the characteristics of patients with primary Sjögren syndrome (pSS) who have autoimmune cytopenia. METHODS: We analyzed 113 participants from the Korean Initiative of Primary Sjögren Syndrome, a prospective pSS cohort. Autoimmune cytopenia was defined as autoimmune origin neutropenia, anemia, and/or thrombocytopenia without vitamin or iron deficiency, or drug-induced cytopenia. To identify the association between autoimmune cytopenia and the clinical characteristics of pSS, extraglandular manifestations were analyzed according to the European League Against Rheumatism Sjögren's syndrome disease activity index (ESSDAI) definition. Xerophthalmia was assessed with the Ocular Surface Disease Index, Schirmer I test, ocular stain score (OSS), and tear film breakup time. RESULTS: The median total ESSDAI score was 2 (interquartile range 1-6). About a quarter of patients had no systemic activity. Autoimmune cytopenia was observed in 23.9% of patients (n = 27). Moderate biological features were more frequently observed in patients with autoimmune cytopenia than in patients without [10 (37%) and 11 (12.8%), respectively, p = 0.016]. Articular involvement was exhibited in 1 patient with autoimmune cytopenia, but in 23 patients (27.4%) without autoimmune cytopenia (p = 0.013). Higher OSS (p = 0.002) and lower mean Schirmer I test (p = 0.029) were observed in patients with autoimmune cytopenia than in those without. Neutrophils and lymphocytes negatively correlated with OSS (ρ = -0.204, p = 0.041 and ρ = -0.230, p = 0.020, respectively). CONCLUSION: Autoimmune cytopenia is closely associated with severe ocular surface damage in pSS. Therefore, assessment of xerophthalmia by ophthalmologists may be mandatory, particularly in patients with pSS with cytopenia, even if patients do not complain of eye dryness.
26440590 Upregulation of long noncoding RNA TMEVPG1 enhances T helper type 1 cell response in patie 2016 Apr Long noncoding RNAs (lncRNA) play key roles in regulating autoimmunity and immunity balance. LncRNA TMEVPG1, which is encoded by a gene located near the Ifn gene, contributes to interferon gamma expression. We investigated the expression of TMEVPG1 in patients with Sjögren syndrome (SS) to determine its role in the pathogenesis of SS. In this study, we detected the relative expression of TMEVPG1 in CD4(+) T cells of 25 SS patients and 25 healthy donors. Moreover, the proportion of Th1 cells and T-bet levels was also analyzed. Furthermore, we explored the correlation between the expression of TMEVPG1 and the level of autoantibodies, erythrocyte sedimentation rate (ESR) and IgG in SS patients. Our results indicated that the proportion of Th1 cells and the levels of TMEVPG1 and T-bet were increased in SS patients. In addition, the level of expression of TMEVPG1 was correlated with the level of SSA, ESR and IgG. Our data suggest that upregulation of lncRNA TMEVPG1 may be involved in the pathogenesis of Sjögren syndrome.
27498447 Fever of unknown origin--diagnostic methods in a European developing country. 2016 Jun BACKGROUND/AIM: Fewer of unknown origin (FUO) remains amongst the most difficult diagnostic dilemmas in contemporary medicine. The aim of this study was to determine the causes of FU and to identify the methods of diagnosis in patients with FUO in a tertiary care setting in the Republic of Macedonia. METHODS: Retrospectively histories of 123 immunocompetent patients older than 14 years with classical FUO that had been examined at the University Hospital for Infectious Diseases and Febrile Conditions in the city of Skopje, during the period 2006-2012 were evaluated. FUO was defined as axillary fever of ≥ 37.5 °C on several occasions, fever duration of more than 21 days and failure to reach the diagnosis after the initial diagnostic workup comprised of several defined basic investigations. RESULTS: Infections were the cause of FUO in 51 (41.5%) of the patients, followed by non-infective inflammatory disorders (NIID) in 28 (22.8%), miscellaneous in 12 (9.7%) and neoplasm in 11 (8.9%) of the patients. Twenty one of the patients (17.1%) remained undiagnosed. The most common causes for FUO were visceral leishmaniasis, abscesses, urinary tract infections, subacute endocarditis, polymyalgia rheumatica and adult onset of Still disease. The final diagnosis was reached with histology in 24 (23.5%), imaging and endoscopic procedures in 21 (20.6%), clinical course and empiric therapy response in 20 (19.6%), serology in 18 (17.6%) and cultures in 16 (15.7%) of the cases. CONCLUSION: In the Republic of Macedonia infections are the leading cause of FUO, predominately visceral leishmaniasis. In the future in patients with prolonged fever, physicians should think more often of this disease, as well as of the possibility of atypical presentation of the common classical causes of FUO.
27243418 Minor salivary glands function is decreased in hyposalivation-related diseases. 2016 Sep OBJECTIVES: The aim of this cross-sectional study was to investigate the relationship between minor salivary gland (MSG) flow rates and oral dryness degrees in patients with xerostomia induced by primary Sjögren's syndrome (pSS), IgG4-related sialadenitis (IgG4-RS), radiation therapy-induced dry mouth (RTDM), or Steven-Johnson syndrome (SJS). DESIGN: 160 patients with pSS, IgG4-RS, RTDM, or SJS and their age- and sex-matched healthy control subjects were enrolled. The whole saliva flow rates and MSG flow rates were measured in four locations, including the upper labial, lower labial, buccal, and palatal mucosae. The degree of oral dryness was assessed in patient groups using the summated xerostomia inventory (SXI). RESULTS: The flow rates of whole saliva and most MSGs in patient groups were significantly lower than the flow rates in healthy control groups (P<0.05). The mean relative percentage of decrease in saliva flow rates was smaller in MSGs than in whole saliva in patient groups (P<0.05), indicating that these disorders have less impact on MSGs. Among the four MSG locations (the upper labial, lower labial, buccal, and palatal), buccal glands showed the highest flow rates in patient groups (P<0.05). SXI scores were significantly higher in pSS and RTDM patients than in IgG4-RS and SJS patients (P<0.05). The degree of xerostomia varied among different patient groups (P<0.05) and there was no clear correlation between MSG flow rates and SXI scores (P>0.05). CONCLUSIONS: MSG function is significantly reduced in pSS, RTDM, IgG4-RS, and SJS patients, but this reduction is more pronounced in the major salivary glands.
25906316 Interaction between innate immunity and Ro52-induced antibody causes Sjögren's syndrome-l 2016 Mar OBJECTIVES: Autoantibodies reactive with Ro52 are often found in sera of patients with Sjögren's syndrome (SS). This study was undertaken to investigate the role of Ro52-induced immune responses in pathogenesis of SS. METHODS: New Zealand Mixed (NZM) 2758 mice were immunised with Ro52 in alum adjuvant. Control mice were immunised either with maltose-binding protein or injected with alum alone. Mice were monitored for anti-Ro52 antibody, sialoadenitis and pilocarpine-induced salivation. Antibody binding to salivary gland (SG) cells was analysed in vivo and in vitro by immunofluorescence. Sera from immunised mice were passively transferred into untreated or alum injected NZM2758 mice. RESULTS: By day 30 post-immunisation, Ro52 immunised mice generated immunoprecipitating anti-Ro52 antibodies and they had the maximum drop in saliva production. Both Ro52 immunised and control mice showed evidence of mild sialoadenitis. However, only Ro52 immunised mice had antibody deposition in their SG. Passive transfer of Ro52-immune sera induced SG dysfunction in recipient mice, only if the recipients were primed with alum. In vitro, antibodies from Ro52-immune sera were internalised by a SG cell line and this uptake was inhibited by cytochalasin D treatment. CONCLUSIONS: Our data show for the first time that antibodies induced by Ro52 are capable of inducing SG dysfunction, and that this phenomenon is dependent on the activation of innate immunity. The mouse model described in this study implies that autoantibody deposition in the SG might be an important step in the induction of xerostomia and pathogenesis of SS.
25572532 The osteopontin transgenic mouse is a new model for Sjögren's syndrome. 2015 Mar Osteopontin (Opn) is a cytokine involved in both physiological and pathological processes, and is elevated in many autoimmune diseases. Sjögren's syndrome (SS) is an autoimmune disease with a strong female predilection characterized by lymphocytic infiltration of exocrine glands. We hypothesized that Opn contributes to SS pathogenesis. We examined an established SS model and found increased Opn locally and systemically. Next, we examined Opn transgenic (Opn Tg) mice for evidence of SS. Opn Tg animals exhibited lymphocytic infiltration of salivary and lacrimal glands, and Opn co-localized with the infiltrates. Moreover, saliva production was reduced, and SS autoantibodies were observed in the serum of these mice. Finally, female Opn Tg mice showed more severe disease compared to males. Taken together, these data support a role for Opn in SS pathogenesis. We identify a new model of spontaneous SS that recapitulates the human disease in terms of sex predilection, histopathology, salivary deficits, and autoantibodies.
27228631 Autoimmune/Inflammatory Syndrome Induced by Adjuvants and Sjögren's Syndrome. 2016 Mar Sjögren's syndrome (SS), a chronic systemic autoimmune inflammatory condition involving the exocrine glands, has been suggested to be part of the spectrum of the Autoimmune/ inflammatory Syndrome Induced by Adjuvants (ASIA). ASIA incorporates an umbrella of clinical conditions including siliconosis, macrophage myofasciitis syndrome, and post-vaccination phenomena that occur after the exposure to a substance, namely the adjuvant. Interestingly, SS and ASIA share several common features. Firstly, a shared pathogenic mechanism involving a disruption of the immune system balance, with B cell proliferation, cytokine production and tissue infiltration, has been proposed. Patients with ASIA often present clinical features resembling those of SS; dry mouth and dry eyes have also been included in the proposed classification criteria for ASIA. Finally, several case reports have suggested that both vaccines and silicone may trigger the development of SS. Unveiling these common pathways will contribute considerably to our understanding and management of both conditions.
26888739 Autoantigen-targeting microRNAs in Sjögren's syndrome. 2016 Apr MicroRNAs are short endogenous non-coding RNAs that regulate gene expression in various physiological and pathological conditions. To characterize autoantigen-targeting microRNAs in Sjögren's syndrome (SS), a systematic study was carried out, in which a candidate microRNA set was first identified by bioinformatics analysis and literature search. Then, their gene silencing activities were evaluated with fusion reporter gene and endogenous targets, leading to the identification of three microRNAs: TRIM21-targeting miR-1207-5p, TRIM21-targeting miR-4695-3p, and La autoantigen-targeting miR-299-5p. Compared to healthy controls, downregulation of miR-1207-5p and miR-4695-3p expression was further revealed in the minor salivary glands of primary SS (pSS) patients. This, on the one hand, characterized two autoantigen-targeting microRNAs in Sjögren's syndrome and, on the other hand, suggested that downregulation of miR-1207-5p and miR-4695-3p expression may lead to increased TRIM21 levels in the minor salivary glands, which contributes to the development of Sjögren's syndrome.